tbuckley/cabot-search huggingface dataset:
Transthyretin cardiac amyloidosis
Authors: Aldostefano Porcari, Marianna Fontana, Julian D Gillmore
Journal: Cardiovascular Research (2022)

Abstract Transthyretin cardiac amyloidosis (ATTR-CA) is an increasingly recognized cause of heart failure (HF) and mortality worldwide. Advances in non-invasive diagnosis, coupled with the development of effective treatments, have shifted ATTR-CA from a rare and untreatable disease to a relatively prevalent condition that clinicians should consider on a daily basis. Amyloid fibril formation results from age-related failure of homoeostatic mechanisms in wild-type ATTR (ATTRwt) amyloidosis (non-hereditary form) or destabilizing mutations in variant ATTR (ATTRv) amyloidosis (hereditary form). Longitudinal large-scale studies in the United States suggest an incidence of cardiac amyloidosis in the contemporary era of 17 per 100 000, which has increased from a previous estimate of 0.5 per 100 000, which was almost certainly due to misdiagnosis and underestimated. The presence and degree of cardiac involvement is the leading cause of mortality both in ATTRwt and ATTRv amyloidosis, and can be identified in up to 15% of patients hospitalized for HF with preserved ejection fraction. Associated features, such as carpal tunnel syndrome, can preceed by several years the development of symptomatic HF and may serve as early disease markers. Echocardiography and cardiac magnetic resonance raise suspicion of disease and might offer markers of treatment response at a myocardial level, such as extracellular volume quantification. Radionuclide scintigraphy with ‘bone’ tracers coupled with biochemical tests may differentiate ATTR from light chain amyloidosis. Therapies able to slow or halt ATTR-CA progression and increase survival are now available. In this evolving scenario, early disease recognition is paramount to derive the greatest benefit from treatment.
A short course of antibiotics is effective for treating pneumonia in children
Authors: Helen Saul, Deniz Gursul, Samantha Cassidy, Julia Bielicki
Journal: BMJ (2022)

The study Barratt S, Bielicki JA, Dunn D, et al. Amoxicillin duration and dose for community-acquired pneumonia in children: the CAP-IT factorial non-inferiority RCT. Health Technol Assess 2021;25:60. To read the full NIHR Alert, go to: https://evidence.nihr.ac.uk/alert/short-course-antibiotics-effective-in-childhood-pneumonia/
Hepatitis of unknown aetiology in children – epidemiological overview of cases reported in Europe, 1 January to 16 June 2022
Authors: Adriana Romaní Vidal, Aisling Vaughan, Francesco Innocenti, Soledad Colombe, Lina Nerlander, Natalia Rachwal, Bruno Christian Ciancio, Aikaterini Mougkou, Carlos Carvalho, Enrique Delgado, Piers Mook, Géraldine de Muylder, Michael Peeters, Tencho Tenev, Elitsa Golkocheva-Markova, Veronika Vorobieva Solholm Jensen, Anders Koch, Julie Figoni, Cécile Brouard, Georgia Nikolopoulou, Anastasia Zisouli, Niamh Murphy, Annemarie Broderick, Lital Goldberg, Rivka Rich, Lior Hecht Sagie, Maria Elena Tosti, Barbara Suligoi, Rosa Joosten, Roan Pijnacker, Ingvild Fjeldheim, Eli Heen, Małgorzata Stępień, Piotr Polański, Rui Tato Marinho, João Vieira Martins, Carmen Varela, Ana Avellón, Emmi Andersson, Marie Jansson Mörk, Sema Mandal, Conall Watson, Laura Coughlan, Meera Chand, Claire Neill, Declan T Bradley, Kathy Li, Maureen O’Leary, Neil McInnes, Christopher J Williams, Catherine Moore, Ardiana Gjini, Erika Duffell, Richard Pebody
Journal: Eurosurveillance (2022)

Following the report of an excess in paediatric cases of severe acute hepatitis of unknown aetiology by the United Kingdom (UK) on 5 April 2022, 427 cases were reported from 20 countries in the World Health Organization European Region to the European Surveillance System TESSy from 1 January 2022 to 16 June 2022. Here, we analysed demographic, epidemiological, clinical and microbiological data available in TESSy. Of the reported cases, 77.3% were 5 years or younger and 53.5% had a positive test for adenovirus, 10.4% had a positive RT-PCR for SARS-CoV-2 and 10.3% were coinfected with both pathogens. Cases with adenovirus infections were significantly more likely to be admitted to intensive care or high-dependency units (OR = 2.11; 95% CI: 1.18–3.74) and transplanted (OR = 3.36; 95% CI: 1.19–9.55) than cases with a negative test result for adenovirus, but this was no longer observed when looking at this association separately between the UK and other countries. Aetiological studies are needed to ascertain if adenovirus plays a role in this possible emergence of hepatitis cases in children and, if confirmed, the mechanisms that could be involved.
Author Correction: Neoadjuvant study of niraparib in patients with HER2-negative, BRCA-mutated, resectable breast cancer
Authors: Laura M. Spring, Hyo Han, Minetta C. Liu, Erika Hamilton, Hanna Irie, Cesar A. Santa-Maria, James Reeves, Peng Pan, Ming Shan, Yongqiang Tang, Julie R. Graham, Sebastien Hazard, Leif W. Ellisen, Steven J. Isakoff
Journal: Nature Cancer (2022)
The Oral Microbiome and Lung Cancer Risk: An Analysis of 3 Prospective Cohort Studies
Authors: Emily Vogtmann, Xing Hua, Guoqin Yu, Vaishnavi Purandare, Autumn G Hullings, Dantong Shao, Yunhu Wan, Shilan Li, Casey L Dagnall, Kristine Jones, Belynda D Hicks, Amy Hutchinson, J Gregory Caporaso, William Wheeler, Dale P Sandler, Laura E Beane Freeman, Linda M Liao, Wen-Yi Huang, Neal D Freedman, Neil E Caporaso, Rashmi Sinha, Mitchell H Gail, Jianxin Shi, Christian C Abnet
Journal: JNCI Journal of the National Cancer Institute (2022)

Abstract Background Previous studies suggested associations between the oral microbiome and lung cancer, but studies were predominantly cross-sectional and underpowered. Methods Using a case-cohort design, 1306 incident lung cancer cases were identified in the Agricultural Health Study; National Institutes of Health-AARP Diet and Health Study; and Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial. Referent subcohorts were randomly selected by strata of age, sex, and smoking history. DNA was extracted from oral wash specimens using the DSP DNA Virus Pathogen kit, the 16S rRNA gene V4 region was amplified and sequenced, and bioinformatics were conducted using QIIME 2. Hazard ratios and 95% confidence intervals were calculated using weighted Cox proportional hazards models. Results Higher alpha diversity was associated with lower lung cancer risk (Shannon index hazard ratio = 0.90, 95% confidence interval = 0.84 to 0.96). Specific principal component vectors of the microbial communities were also statistically significantly associated with lung cancer risk. After multiple testing adjustment, greater relative abundance of 3 genera and presence of 1 genus were associated with greater lung cancer risk, whereas presence of 3 genera were associated with lower risk. For example, every SD increase in Streptococcus abundance was associated with 1.14 times the risk of lung cancer (95% confidence interval = 1.06 to 1.22). Associations were strongest among squamous cell carcinoma cases and former smokers. Conclusions Multiple oral microbial measures were prospectively associated with lung cancer risk in 3 US cohort studies, with associations varying by smoking history and histologic subtype. The oral microbiome may offer new opportunities for lung cancer prevention.
Publisher Correction: Efficient in vivo base editing via single adenoassociated viruses with size-optimized genomes encoding compact adenine base editors
Authors: Jessie R. Davis, Xiao Wang, Isaac P. Witte, Tony P. Huang, Jonathan M. Levy, Aditya Raguram, Samagya Banskota, Nabil G. Seidah, Kiran Musunuru, David R. Liu
Journal: Nature Biomedical Engineering (2022)
What can we learn from the first 100 days of the monkeypox outbreak?
Authors: Jeffrey S. Crowley, Gregorio A. Millett, Lawrence O. Gostin
Journal: BMJ (2022)

To evaluate the use of plasma haptoglobin (Hp) levels and N-terminal pro-B-type natriuretic peptide (NT-proBNP) in predicting survival in patients with severe acute decompensated heart failure (AHF). Management of AHF is challenging. Identifying markers associated with patient prognosis in this disease is clinically important. In this prospective observational study, plasma Hp and NT-proBNP levels were measured. Receiver operating characteristic (ROC) curves were used to identify cut-offs of Hp and NT-proBNP with the greatest specificity and sensitivity for predicting overall survival and cardiovascular-related survival. The cut-off values were tested in patients with AHF (n=41). The cut-off value with the greatest specificity and sensitivity with respect to overall survival and for cardiovascular-related survival for Hp was 177. 1 ng/mL for both outcomes and for NT-proBNP was 34 246.0 pg/mL and 11 848.5 ng/mL, respectively. Using these cut-off values, this study found that patients with lower baseline Hp levels (&lt;177. 1 ng/mL) or higher baseline NT-proBNP (≥34 246 pg/mL) were more likely to have shorter overall survival. Similarly, patients with &lt;177. 1 ng/mL of Hp and ≥11 848.5 pg/mL of NT-proBNP had the highest risk of death related to cardiovascular disease. Our findings indicate that Hp and NT-proBNP using specific cut-off values for AHF can be used to determine risk of survival in these patients.
Antigenic cartography using sera from sequence-confirmed SARS-CoV-2 variants of concern infections reveals antigenic divergence of Omicron
Authors: Karlijn van der Straten, Denise Guerra, Marit J. van Gils, Ilja Bontjer, Tom G. Caniels, Hugo D.G. van Willigen, Elke Wynberg, Meliawati Poniman, Judith A. Burger, Joey H. Bouhuijs, Jacqueline van Rijswijk, Wouter Olijhoek, Marinus H. Liesdek, A.H. Ayesha Lavell, Brent Appelman, Jonne J. Sikkens, Marije K. Bomers, Alvin X. Han, Brooke E. Nichols, Maria Prins, Harry Vennema, Chantal Reusken, Menno D. de Jong, Godelieve J. de Bree, Colin A. Russell, Dirk Eggink, Rogier W. Sanders
Journal: Immunity (2022)

Large-scale vaccination campaigns have prevented countless hospitalizations and deaths due to COVID-19. However, the emergence of SARS-CoV-2 variants that escape from immunity challenges the effectiveness of current vaccines. Given this continuing evolution, an important question is when and how to update SARS-CoV-2 vaccines to antigenically match circulating variants, similarly to seasonal influenza viruses where antigenic drift necessitates periodic vaccine updates. Here, we studied SARS-CoV-2 antigenic drift by assessing neutralizing activity against variants of concern (VOCs) in a set of sera from patients infected with viral sequence-confirmed VOCs. Infections with D614G or Alpha strains induced the broadest immunity, whereas individuals infected with other VOCs had more strain-specific responses. Omicron BA.1 and BA.2 were substantially resistant to neutralization by sera elicited by all other variants. Antigenic cartography revealed that Omicron BA.1 and BA.2 were antigenically most distinct from D614G, associated with immune escape, and possibly will require vaccine updates to ensure vaccine effectiveness.
Ethnic disparities in out-of-hospital cardiac arrest: A population-based cohort study among adult Danish immigrants
Authors: Rodrigue Garcia, Deepthi Rajan, Peder Emil Warming, Jesper Svane, Christoffer Vissing, Peter Weeke, Carlo Alberto Barcella, Reza Jabbari, Gunnar Hilmar Gislason, Christian Torp-Pedersen, Jørgen Holm Petersen, Fredrik Folke, Jacob Tfelt-Hansen
Journal: The Lancet Regional Health - Europe (2022)

Ethnicity might impact out-of-hospital cardiac arrest (OHCA) risk, but it has scarcely been studied in Europe. We aimed to assess whether ethnicity influenced the risk of OHCA of cardiac cause in Danish immigrants and its interplay with risk factors for OHCA and socioeconomic status.This nationwide study included all immigrants between 18 and 80 years present in Denmark at some point between 2001 and 2020. Regions of origin were defined as Africa, Arabic countries, Asia, Eastern Europe, Latin America, and Western countries. OHCAs with presumed cardiac cause were identified from the Danish Cardiac Arrest Registry.Overall, among 1,011,565 immigrants, a total of 1,801 (0.2%) OHCAs (median age 64 (Q1-Q3 53-72) years, 72% males) occurred. The age- and sex- standardized (reference: Western countries) incidence of OHCA (/1,00,000 person-years) was 34.6 (27.8-43.4) in African, 34.1 (30.4-38.4) in Arabic, 33.5 (29.3-38.2) in Asian, 35.6 (31.9-39.6) in Eastern European, and 16.2 (9.0-27.2) in Latin American immigrants. When selecting Western origin as a reference, and after adjusting on OHCA risk factors, Arabic (HR 1.18, 95%CI 1.04-1.35; P=0.01), Eastern European (HR 1.28, 95%CI 1.13-1.46; P<0.001), and African origin (HR 1.34, 95%CI 1.10-1.63; P<0.01) were associated with higher risk of OHCA, whereas Latin American origin (HR 0.58, 95%CI 0.35-0.0.96; P=0.03) was associated with lower risk of OHCA. Comparable results were observed when adjusting on education level and economic status.This study emphasizes that ethnicity is associated with OHCA risk, even when considering traditional cardiac arrest risk factors.R Garcia received a grant from the Fédération Française de Cardiologie for his post-doctoral fellowship and this work was supported by the Novo Nordisk Foundation Tandem Programme 2022 (grant# 31364).
Bacteria-mediated metformin-loaded peptide hydrogel reprograms the tumor immune microenvironment in glioblastoma
Authors: Lisheng Zhu, Jingyu Liu, Mengjun Qiu, Jiayuan Chen, Qing Liang, Gang Peng, Zhenwei Zou
Journal: Biomaterials (2022)

The tumor immune microenvironment (TIME) is one of the significant hallmarks of cancer and has the important role of largely determining the malignancy level of tumors. As an approach to break through this bottleneck of tumor treatment methods, the TIME can be reprogrammed by certain nanomaterials. Here, we coated C-novyi-spores with melittin-RADA32 nanofiber hybrid peptide and loaded the immunomodulator metformin to obtain MRM-coated spores as a powerful antitumor nanodrug against glioblastoma (GBM), which is based on the activation of the TIME. MRM-coated spores exhibit extended-release profiles and an enhanced killing effect on GBM both in vitro and in vivo. Furthermore, MRM-coated spores can educate the innate and adaptive immune system by inducing sustainable CD8+ T cell responses, promoting M1 macrophage polarization, and regulating the expression of HIF1-α, PDL1, and CXCL9 in TIME. In intracranial applications, MRM-coated spores showed excellent biosafety and a strong therapeutic effect. In summary, peptide hydrogels provide a promising strategy in which advantages of different treatment methods can be incorporated to synthesize potent antitumor drugs with mild side effects from bacteria-mediated nanomaterials.
Combined immunosuppression for acquired hemophilia A: CyDRi is a highly effective low-toxicity regimen
Authors: Barbara Simon, Andrea Ceglédi, János Dolgos, Péter Farkas, Manila Gaddh, László Hankó, Robert Horváth, Ambrus Kaposi, Lászlóné Magyar, Tamás Masszi, Attila Szederjesi, Nikolett Wohner, Imre Bodó
Journal: Blood (2022)

Acquired hemophilia A (AHA) is a rare severe autoimmune bleeding disorder with significant morbidity and mortality. Although critical for disease control, there is no consensus for the best immunosuppressive regimen. Most authors use steroids first line, followed by other agents for steroid failures. Upfront combined regimens offer the advantage of reduced steroid exposure and toxicity as well as increased efficacy. We retrospectively analyzed data from 32 patients with AHA treated on an identical such institutional protocol: cyclophosphamide 1000 mg on days 1 and 22, dexamethasone 40 mg on days 1, 8, 15, and 22, and rituximab 100 mg on days 1, 8, 15, and 22 (the regimen was termed CyDRi). All patients received at least 1 cycle of CyDRi. If necessary, CyDRi was repeated until remission, no sooner than day 43 of the previous cycle. Bleeding control was rapidly achieved. The median time for bleeding control was 15.5 days (range, 0-429 days; interquartile range, 2.5-29.5 days). Thirty-one (96.8%) of 32 patients achieved durable complete remission (CR); 29 (90.6%) of 32 patients were alive at last follow-up, all of them in CR. The median time to reach first CR was 77 days (range, 19-939 days; interquartile range, 31-115 days). Toxicity and side effects were acceptable and milder than those of commonly used, prolonged steroid therapies. In conclusion, the CyDRi regimen produced markedly higher CR rates and overall survival than currently used sequential regimens. Taken together, CyDRi proved to be an attractive option for the immunosuppression of elderly patients with AHA.
Hepatocyte leukotriene B4 receptor 1 promotes NAFLD development in obesity
Authors: Xingfeng Liu, Kai Wang, Luhai Wang, Lijuan Kong, Shaocong Hou, Yanjun Wan, Chunxiao Ma, Jingwen Chen, Xiaowei Xing, Caiyi Xing, Qian Jiang, Qijin Zhao, Bing Cui, Zhifeng Huang, Pingping Li
Journal: Hepatology (2022)

NAFLD is the most prevalent chronic liver disease worldwide and has emerged as a serious public health issue with no approved treatment. The development of NAFLD is strongly associated with hepatic lipid content, and patients with NAFLD have significantly higher rates of hepatic de novo lipogenesis (DNL) than lean individuals. Leukotriene B4 (LTB4), a metabolite of arachidonic acid, is dramatically increased in obesity and plays important role in proinflammatory cytokine production and insulin resistance. But the role of liver LTB4/LTB4 receptor 1 (Ltb4r1) in lipid metabolism is unclear.Hepatocyte-specific knockout (HKO) of Ltb4r1 improved hepatic steatosis and systemic insulin resistance in both diet-induced and genetically induced obese mice. The mRNA level of key enzymes involved in DNL and fatty acid esterification decreased in Ltb4r1 HKO obese mice. LTB4/Ltb4r1 directly promoted lipogenesis in HepG2 cells and primary hepatocytes. Mechanically, LTB4/Ltb4r1 promoted lipogenesis by activating the cAMP-protein kinase A (PKA)-inositol-requiring enzyme 1α (IRE1α)-spliced X-box-binding protein 1 (XBP1s) axis in hepatocytes, which in turn promoted the expression of lipogenesis genes regulated by XBP1s. In addition, Ltb4r1 suppression through the Ltb4r1 inhibitor or lentivirus-short hairpin RNA delivery alleviated the fatty liver phenotype in obese mice.LTB4/Ltb4r1 promotes hepatocyte lipogenesis directly by activating PKA-IRE1α-XBP1s to promote lipogenic gene expression. Inhibition of hepatocyte Ltb4r1 improved hepatic steatosis and insulin resistance. Ltb4r1 is a potential therapeutic target for NAFLD.
Understanding COVID-19-associated coagulopathy
Authors: Edward M. Conway, Nigel Mackman, Ronald Q. Warren, Alisa S. Wolberg, Laurent O. Mosnier, Robert A. Campbell, Lisa E. Gralinski, Matthew T. Rondina, Frank L. van de Veerdonk, Karin M. Hoffmeister, John H. Griffin, Diane Nugent, Kyung Moon, James H. Morrissey
Journal: Nature reviews. Immunology (2022)
Interim Guidance for Prevention and Treatment of Monkeypox in Persons with HIV Infection — United States, August 2022
Authors: Jesse O’Shea, Thomas D. Filardo, Sapna Bamrah Morris, John Weiser, Brett Petersen, John T. Brooks
Journal: MMWR Morbidity and Mortality Weekly Report (2022)

Monkeypox virus, an orthopoxvirus sharing clinical features with smallpox virus, is endemic in several countries in Central and West Africa. The last reported outbreak in the United States, in 2003, was linked to contact with infected prairie dogs that had been housed or transported with African rodents imported from Ghana (1). Since May 2022, the World Health Organization (WHO) has reported a multinational outbreak of monkeypox centered in Europe and North America, with approximately 25,000 cases reported worldwide; the current outbreak is disproportionately affecting gay, bisexual, and other men who have sex with men (MSM) (2). Monkeypox was declared a public health emergency in the United States on August 4, 2022.† Available summary surveillance data from the European Union, England, and the United States indicate that among MSM patients with monkeypox for whom HIV status is known, 28%-51% have HIV infection (3-10). Treatment of monkeypox with tecovirimat as a first-line agent is available through CDC for compassionate use through an investigational drug protocol. No identified drug interactions would preclude coadministration of tecovirimat with antiretroviral therapy (ART) for HIV infection. Pre- and postexposure prophylaxis can be considered with JYNNEOS vaccine, if indicated. Although data are limited for monkeypox in patients with HIV, prompt diagnosis, treatment, and prevention might reduce the risk for adverse outcomes and limit monkeypox spread. Prevention and treatment considerations will be updated as more information becomes available.
Population based study of risk factors for underdiagnosis of asthma in adolescence: Odense schoolchild study Commentary: Risk factors for underdiagnosis of asthma in adolescence Commentary: Identifying the correct risks in diagnosis Commentary: Improving the diagnostic rate in asthma: a community issue
Authors: H. C Siersted, J. Boldsen, H. S Hansen, G. Mostgaard, N. Hyldebrandt, P J. Rees, S. J W Evans, H. C Siersted
Journal: BMJ (1998)

<h3>Abstract</h3> <b>Objective:</b> To describe factors related to underdiagnosis of asthma in adolescence. <b>Design:</b> Subgroup analysis in a population based cohort study. <b>Setting:</b> Odense municipality, Denmark. <b>Subjects:</b> 495 schoolchildren aged 12 to 15 years were selected from a cohort of 1369 children investigated 3 years earlier. Selection was done by randomisation (n=292) and by a history indicating allergy or asthma-like symptoms in subject or family (n=203). <b>Main outcome measures:</b> Undiagnosed asthma defined as coexistence of asthma-like symptoms and one or more obstructive airway abnormalities (low ratio of forced expiratory volume in 1 second to forced vital capacity, hyperresponsiveness to methacholine or exercise, or peak flow hypervariability) in the absence of physician diagnosed asthma. Risk factors (odds ratios) for underdiagnosis. <b>Results:</b> Undiagnosed asthma comprised about one third of all asthma identified. Underdiagnosis was independently associated with low physical activity, high body mass, serious family problems, passive smoking, and the absence of rhinitis. Girls were overrepresented among undiagnosed patients with asthma (69%) and underrepresented among diagnosed patients (33%). Among the risk factors identified, low physical activity and problems in the family were independently associated with female sex. The major symptom among those undiagnosed was cough (58%), whereas wheezing (35%) or breathing trouble (50%) was reported less frequently than among those diagnosed. Less than one third of those undiagnosed had reported their symptoms to a doctor. <b>Conclusions:</b> Asthma, as defined by combined symptoms and test criteria, was seriously underdiagnosed among adolescents. Underdiagnosis was most prevalent among girls and was associated with a low tendency to report symptoms and with several independent risk factors that may help identification of previously undiagnosed asthmatic patients. <h3>Key messages</h3> One third of young people with asthma are not diagnosed; most are girls Undiagnosed asthma is associated with low physical activity, high body mass index, serious family problems, passive smoking, and the absence of symptoms of rhinitis Cough is the most common symptom among those with undiagnosed asthma Two thirds of those with undiagnosed asthma do not report their symptoms to a doctor, suggesting a need for targeted asthma campaigns